Ethnicity Greatly Influences Cytokine Gene Polymorphism Distribution (original) (raw)
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Iranian journal of kidney diseases
Single nucleotide polymorphisms within promoter or other regulatory sequences of cytokine genes mainly influence the level of production and secretion of proteins. A large amount of evidence has shown that cytokine gene variations alter graft survival length after kidney transplantation. We studied the association of gene polymorphisms in the interlekin-10 gene (IL10; -1082 G/A), interferon-gamma gene (IFNG; +874 T/A), transforming growth factor-beta gene (TGFB; +869 T/C), and tumor necrosis factor-alpha gene (TNFA; -308 A/G) with kidney allograft survival. The IL10 (-1082 G/A), IFNG (+874 T/A), TGFB (+869 T/C), and TNFA (-308 A/G) genotypes were determined in 32 kidney allograft recipients with graft rejection during the 1st posttransplant year and 52 without rejection in 5 posttransplant years, using allele-specific oligonucleotides-polymerase chain reaction method. The IFNG +874 A/T genotype showed a significantly higher frequency among kidney recipients of the rejection group th...
Molecular Biology Reports, 2012
Acute rejection is a common phenomenon in transplantation. Inflammatory and anti-inflammatory mediators affect the graft microenvironment. Th1 responses cause acute rejection while Th2 immune responses help the survival of the graft. In this study, we evaluated gene polymorphisms of IL-6 G-174C, TGF-b T?869C, IL-4 C-590T, and IFN-c T?874A cytokines in renal transplant patients. ARMS-PCR method was used to characterize IL-6 G-174C (rs76144090), TGF-b T?869C (rs1800471), and IFN-c T?874A (rs2430561) polymorphisms and PCR-RFLP, for characterization of IL-4 C-590T (rs2243250) in 100 renal transplant patients. Acute rejection episodes were diagnosed according to the standard criteria. Analysis of the results showed that IL-6-174 GG genotype (P = 0.018, OR = 3.023, 95% CI = 1.183-7.726) and IL-6-174G allele (P = 0.046, OR = 2.114, 95% CI = 1.005-4.447) were more frequent, but IL-6-174GC genotype was less frequent in acute rejection of kidney transplantation in comparison with control group (P = 0.024, OR = 0.302, 95% CI = 0.103-0.883). IFN-c?874 T allele was associated with a higher risk of acute rejection (P = 0.019, OR = 2.088, 95% CI = 1.124-3.880) while IFN-c?874 AA genotype was associated with a lower risk of rejection (P = 0.023, OR = 0.318, 95% CI = 0.115-0.875). Frequencies of TGF-b T?869C and IL-4 C-590T were not significantly different (P [ 0.05). Consequently, our results show that IL-6 G-174C and IFN-c T?874A gene polymorphisms have predictive values for acute rejection after renal transplantation in Iranian patients.
Transplant Immunology, 2001
Cytokines are key immune mediators and it has been suggested that cytokine gene polymorphisms affecting expression influence rejection or tolerance. This study sought to examine this hypothesis with the aim of identifying predictive genotype markers for rejection. The study group consisted of 120 consecutive first cadaveric recipient᎐donor pairs transplanted at a single Ž U U significantly increased in the rejector group Ps 0.02. Also, the combination of recipient IL-10 A negativerdonor IL-10 A Ž. Ž. positive recipient high producerrdonor low producer , was significantly decreased in multiple rejectors Ps 0.04. No significant associations were detected between TNF-␣ and TGF-1, and rejection. This study suggests that the combination of recipient᎐donor IL-4 and IL-10 genotypes may be important in renal transplantation outcome. The results appear to corroborate the protective role of both of these cytokines, possibly due to their ability to suppress inflammation. However, due to conflicting results from this and other studies, a multi-centre collaborative study may be required to determine whether cytokine genotypes are significant, independent predictors of renal allograft rejection.
Nephrology Dialysis Transplantation, 2008
Background. Cytokine gene polymorphisms have been associated with poor outcomes after renal transplantation such as chronic allograft nephropathy (CAN), graft rejection (GR) and graft failure (GF), but the effects of these polymorphisms are still controversial. We therefore conducted a systematic review, with individual patient data (IPD) where possible, to determine the association between cytokine polymorphisms (TGF-β1, TNF-α and IL-10) and outcomes after renal transplantation. Methods. Five investigators were willing to participate and provided IPD. The outcomes of interest were GF, GR and CAN. Subjects with at least one of these were classified as having poor outcomes. Heterogeneity of gene effects was assessed. Multiple logistic regression was applied to assess gene effects, adjusting for clinical variables such as HLA matching and age. Results. One-thousand and eighty-seven subjects were included in the IPD meta-analysis. Pooled results showed no evidence of heterogeneity and indicated that the strongest variables determining poor outcomes are HLA mismatching (OR = 1.6-1.8 for ≥3 HLA-A, -B, -DR mismatches compared with those with <3 mismatches) and age (OR = 1.2-1.4 for age 45 years or more). Incremental information on risk of a poor outcome is provided by the TGF-β1c10 polymorphism (OR = 1.5, P = 0.034, 95% CI: 1.0-2.2 for TC genotype compared to TT genotype). Haplotypes of TGF-β1 at c10 and c25 were inferred and the C-C haplotype was a marker of a poor outcome (OR = 1.3, P = 0.177, 95% CI: 1.0-2.3). Three polymorphisms of the IL-10 gene Correspondence and offprint requests to: Ammarin Thakkinstian, Clinical Epidemiology Unit, at −1082, −819, −592 are in strong linkage disequilibrium with each other (correlation coefficients: 0.6-1) and inferred haplotypes between these three loci show some association, with ACC increasing the risk of poor events compared to GCC (OR = 1.3, P = 0.044, 95% CI: 0.9-1.6). Conclusion. Pooled results to date suggest possible association between both the TGF-β1 c10 polymorphism and a 3-SNP-haplotype of IL-10 and poor outcomes in renal transplantation, but this needs to be confirmed in larger studies.
Different allelic frequencies of several cytokine genes in Hong Kong Chinese and Swedish Caucasians
Genes and Immunity, 2001
It has been shown that cytokine gene polymorphisms are important in the regulation of the level of cytokine production that may affect the development and extent of inflammatory diseases and transplant rejections. The frequency of the -308 TNFA, -383 TNFR1, -1087 IL10 and codon 25 TGFB1 alleles were analysed in two different ethnic groups: Chinese from Hong Kong and Caucasians from western Sweden. Significant differences in the occurrence of the analysed alleles were shown between the two populations. The most profound difference was found in the frequency of the A/A genotype at the -1087 position of IL10 gene (18% in Caucasians and 89% in Chinese, P &amp;lt; 0.0001, both for the genotype and allele frequencies) and less although statistically significant for other investigated genes. The noted differences in the frequency of functionally important alleles of cytokine genes may have consequences for the mode of appearance and outcome of certain diseases in individuals of different ethnicity.
Transplantation Proceedings, 2012
Background. Certain cytokine gene polymorphisms (CGPs) have been shown to be associated with renal transplant rejection episodes or graft outcomes. We sought to evaluate the relationships between gene polymorphisms and acute rejection episodes (RG, n ϭ 19) versus stable graft function (NRG, n ϭ 71) in transplant recipients compared with healthy control subjects (HCG, n ϭ 150). The follow-up time period was 18 months. Using polymerase chain reaction sequence-specific primers with the Heidelberg kit we genotyped 22 single nucleotide polymorphisms distributed across 13 cytokine and cytokine receptor genes. Results. Interleukin (IL)-2 TT/GT haplotype was found in 36.8% of RG patients and 6.7% of HCG but not among the NRG (P Ͻ .0001; .0007). The IL-2 GG/TT haplotype was observed among 13 NRG and nine HCG patients (P ϭ .007); the IL-2 GG/GG haplotype, 18.7% HCG and 4.2% NRG patients (P ϭ .0033); and the IL-2 TT/TT haplotype, five NRG and eight HCG patients, but none of the RG cohort (P Ͼ .05). The transforminggrowth factor-beta 1 CG/CC haplotype was noted in 15 NRG (21.1%) and four HCG but no RG patients (P Ͻ .0001). The IL-2 ϩ166 GT genotype was detected in 36.8% of RG, 8.5% of NRG, and 14.7% of HCG patients (P ϭ .005, .0244). The IL-2 Ϫ330 GG genotype was demonstrated in 32 healthy controls and three nonrejection transplant patients (P ϭ .0007). Significant differences were concluded between NRG and HCG for IL-6 565 AG, IL-1beta Ϫ511 TT and ϩ3962 CC/CT/TT genotypes. Discussion. We observed significant differences among the frequencies of IL-2 gene polymorphisms among RG and NRG subjects, which agreed with previous clinical, but not in vitro studies.
Renal allograft immune response is influenced by patient and donor cytokine genotypes
Transplantation proceedings
This study investigated the impact of specific cytokine genotypes on the incidence of acute rejection episodes (ARE), chronic graft dysfunction (CGD), and anti-HLA donor-specific antibody (DS-Ab) production in 86 renal transplant recipients and 70 cadaveric donors. A PCR-SSP method was performed for the analysis of polymorphisms in TNF-alpha, IL-6, TGF-beta, IL-10, and IFN-gamma cytokines. DS-Ab monitoring of sera was performed using a FCXM analysis. Observed cytokine frequencies for patients and donors were not significantly different from the expected frequencies under Hardy-Weinberg equilibrium conditions. The evaluation in recipients revealed a higher frequency of DS-Ab-positive patients among the TNF-alpha high (50.0% vs 25.7%), and for the IL-10 cytokine a greater incidence of ARE-positive patients (35.8% vs 18.2%) with the high + intermediate, compared with the low genotype. The combined effect of these 2 genotypes predisposed to DS-Abs (71.4% vs 25.3%; P = 0.02; odds ratio [...